From the Guidelines
Drugs that can increase lactate levels include metformin, nucleoside reverse transcriptase inhibitors (NRTIs) used in HIV treatment, linezolid, propofol, epinephrine, albuterol, and alcohols like ethanol and propylene glycol. These medications can elevate lactate by interfering with mitochondrial function, increasing glycolysis, or altering the body's ability to clear lactate. The risk of drug-induced lactate elevation is higher in patients with renal impairment, liver dysfunction, and critically ill patients, as noted in studies such as 1 and 1. Monitoring lactate levels is crucial when using these medications, especially in high-risk patients or when multiple lactate-elevating drugs are used simultaneously. Some key points to consider include:
- Metformin inhibits complex I of the electron transport chain, shifting metabolism toward anaerobic pathways that produce lactate, as discussed in 1.
- NRTIs, such as zidovudine and stavudine, can cause mitochondrial toxicity, leading to lactic acidosis, as reported in 1 and 1.
- Linezolid, particularly with prolonged use, can increase lactate levels, as mentioned in the example answer.
- Propofol, especially during prolonged infusions, can also elevate lactate, as noted in the example answer.
- Epinephrine, albuterol, and other beta-agonists can increase lactate by increasing glycolysis, as discussed in the example answer.
- Alcohols, including ethanol and propylene glycol, can alter the body's ability to clear lactate, leading to elevated levels, as mentioned in the example answer. It is essential to be aware of these potential lactate-elevating effects when prescribing or administering these medications, especially in vulnerable patient populations, and to monitor lactate levels accordingly, as recommended in 1 and 1.
From the FDA Drug Label
5 WARNINGS AND PRECAUTIONS
- 1 Lactic Acidosis There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk.
Drugs that can increase lactate levels:
- Metformin: can increase lactate blood levels by decreasing liver uptake of lactate, which may increase the risk of lactic acidosis, especially in patients at risk 2. Key factors that increase the risk of metformin-associated lactic acidosis include:
- Renal impairment
- Drug interactions that impair renal function or increase metformin accumulation
- Age 65 or greater
- Radiologic studies with contrast
From the Research
Drugs that Can Increase Lactate Levels
- Metformin: a commonly used treatment for type 2 diabetes mellitus, has been associated with lactic acidosis, particularly in cases of overdose 3 or with predisposing conditions such as renal failure 4.
- Nucleoside/nucleotide reverse transcriptase inhibitors: have been linked to lactic acidosis, although the pathophysiology and incidence have been well established for these agents 5.
- Epinephrine and albuterol: were identified as the most commonly associated agents with medication-induced lactate level elevations in a systematic review of the literature 5.
- Other medications: a total of 59 unique medications were identified as potential causes of medication-induced lactate level elevations, including FDA-labeled doses, intentional overdoses, and prescribed doses exceeding the FDA-labeled dose 5.
Mechanisms and Risk Factors
- Mitochondrial complex I inhibition: Metformin has been shown to inhibit mitochondrial complex I activity, a potential mechanism for lactate accumulation 4.
- Renal impairment: patients with renal impairment are at increased risk of lactic acidosis with Metformin use 4.
- Contraindications: certain conditions, such as cardiovascular, renal, hepatic, and pulmonary disease, and advancing age, may increase the risk of lactic acidosis with Metformin use 6.